Using both clinical and experimental approaches, we propose to study the alteration of the blood-retinal barrier (BRB) which occurs in the early stages of retinal involvement in diabetes. Vitreous fluorophotometry (V.F.) will be further standardized in normals and in diabetes as a routine procedure for evaluation of the BRB in retinal disease. Intraocular fluorescein dynamics and the alteration of the BRB in experimental diabetes will be studied by kinetic V.F. and direct sampling of the vitreous using micromethods. Experimental situations of selective alteration of the BRB transport processes are compared to experimental situations of alteration of the junctional structures. In experimental diabetes, an attempt will be made to correlate the alteration of the BRB with experimentally induced variations in insulin, glucagon, and growth hormone. Finally, in a series of longitudinal and short-term clinical studies, insulin-dependent and noninsulin-dependent diabetic patients will be examined by V.F. and the values obtained compared with degree of diabetic metabolic control and development of retinal lesions.